PLASMA AND PITUITARY THYROID-STIMULATING HORMONE LEVELS IN BROMOCRIPTINE-TREATED NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

1. The effects of a 13-day intraperitoneal (i.p.) infusion of bromocriptine, delivered by osmotic pump, on plasma and pituitary thyroid-stimulating hormone (TSH) levels were investigated in New Zealand genetically hypertensive (GH) rats and their normotensive (NT) controls. 2. In both the GH and NT rats, bromocriptine significantly reduced plasma TSH level but did not have any significant effect on pituitary TSH content. 3. No significant difference was found in the plasma TSH level and pituitary TSH content between the vehicle-treated GH and NT rats. 4. These results suggest that there are no differences between the GH and NT rats with regard to the activity of the central dopaminergic system influencing TSH release and also that TSH does not play a role in the hypertension of the GH rats.     

BLOOD PRESSURE, PLASMA AND PITUITARY PROLACTIN RESPONSES TO BROMOCRIPTINE IN NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls. 2. In the GHR, the mean BP in the BRC-treated group over the 13 day period of study was significantly lower than in the vehicle-treated group. In the NT rats, the mean BP in the BRC-treated group over the 13 day period was also significantly lower than in the vehicle-treated group. 3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC-treated group than in the vehicle-treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC-treated group was, however, not significantly different from that in the vehicle-treated group. 4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC-treated GHR than in the BRC-treated NT rats compared with their respective vehicle-treated groups. 5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hypertension of the GHR.     

PLASMA AND PITUITARY PROLACTIN AND BLOOD PRESSURE IN BROMOCRIPTINE-TREATED SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.     

EFFECT OF ENALAPRIL ON BODY SODIUM AND HANDLING OF A SODIUM CHLORIDE LOAD IN HYPERTENSIVE AND NORMOTENSIVE RATS

1. The effect of enalapril on handling of an Na load and on body Na during 96 h of zero Na intake was measured in hypertensive rats (GH and SHR) and their normotensive controls (N and WKY) by a whole body counting method. 2. Enalapril treatment led to a greater fall in body Na in the first 24 h after the Na load (as expected from the known effect of ACE inhibition on aldosterone production) and thus to a slightly faster excretion of an amount equivalent to the load. 3. Enalapril-treated rats were unable to maintain body Na on a zero Na intake. This was also expected from the known effect on aldosterone production, though other mechanisms are not excluded. The effect was more marked in the SHR and WKY than in GH and N but there was no significant difference in this effect between the hypertensives and their respective control strains.     

Salt and water intake and sodium and potassium excretion in spontaneously hypertensive rats

1. Total fluid and saline intakes were greater in spontaneously hypertensive rats (SHR) than in normotensive rats (NTR). 2. Total fluid and saline intake were significantly elevated in prehypertensive SHR, 5 weeks old, compared with age-matched NTR, and the intakes fell with age in both strains but remained considerably greater in SHR. 3. In SHR, in which the blood pressure was maintained at normotensive levels by treatment with hydralazine, the saline and fluid intakes remained elevated above those of NTR. 4. SHR and NTR fed low sodium diet with water alone to drink have similar excretion rates of sodium, suggesting that their ability to conserve sodium was normal. 5. Measurement of sodium excretion after three different levels of sodium loading, on normal or low sodium diets, also failed to demonstrate an abnormality of renal function in SHR. 6. These results demonstrate that the fluid and saline intakes of SHR are elevated compared with NTR and this difference is independent of the hypertension in SHR and is not secondary to enhanced renal sodium loss.     

INVOLVEMENT OF SYMPATHETIC NERVOUS SYSTEM INHIBITION IN THE HYPOTENSIVE EFFECT OF BROMOCRIPTINE IN SPONTANEOUSLY HYPERTENSIVE RATS

The hypotensive effect of bromocriptine in young (6 week old) spontaneously hypertensive rats (SHR) was studied. Blood pressure and plasma norepinephrine level in bromocriptine-treated SHR were significantly lower than those in vehicle-treated SHR after 3 weeks of treatment (5 mg/kg per day, i.p.), while no significant decrease of blood pressure or plasma norepinephrine level was observed after 2 weeks of treatment. These results suggest the involvement of sympathetic nervous system inhibition in the hypotensive effect of bromocriptine in SHR.     

NITRIC OXIDE SYNTHASE INHIBITION WITH Nω-NITRO-L- ARGININE METHYL ESTER AFFECTS BLOOD PRESSURE AND CARDIOVASCULAR STRUCTURE IN THE GENETICALLY HYPERTENSIVE RAT STRAIN

1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide synthase (NOS) inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME) was used as a tool to investigate further a possible endothelial defect in the New Zealand genetically hypertensive (GH) rat strain compared with its normotensive (N) control strain. 2. N^ω-nitro-L-arginine methyl ester was given to GH and N groups in their drinking water from age 7–10 weeks (10 mg/kg per day for weeks 1 and 2 and then 5 mg/kg per day for week 3). Tail-cuff blood pressure (BP) was measured weekly and at the end of the experiment the mesentery was fixed by perfusion, second order branches of the mesenteric artery were embedded in Technovit and stained sections were used to quantify the structure of the mesenteric resistance arteries (MRA). The heart was removed and weighed for determination of left ventricular (LV) mass. 3. In GH rats, BP and LV mass were significantly raised by L-NAME, while in N rats L-NAME treatment significantly elevated BP, but had no effect on LV mass. 4. In GH rats, the media width was significantly increased by L-NAME treatment (P < 0.01) lumen diameter remained unchanged. Thus, the ratio of media width/lumen diameter (M/L) was significantly increased by exacerbation of the hypertrophic outward remodelling characteristic of the GH strain. There were no significant changes in the M/L ratio in L -NAME-treated N rats. 5. Thus, in the GH strain, cardiovascular structure is more sensitive to NOS inhibition than either its N control strain or (on evidence from the literature) the spontaneously hypertensive rat strain.     

HYPOTENSIVE ACTIVITY OF AQUEOUS EXTRACT OF ANDROGRAPHIS PANICULATA IN RATS

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood presure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract-and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.     

Reduction of Food Intake by Fenofibrate is Associated with Cholecystokinin Release in Long-Evans Tokushima Rats

Fenofibrate is a selective peroxisome proliferator-activated receptor α (PPARα) activator and is prescribed to treat hyperlipidemia. The mechanism through which PPARα agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.     

Effect of beta-adrenergic antagonists on experimentally induced drinking in female rats

The nonspecific beta-adrenergic antagonist d,l propranolol, the specific beta 1-adrenergic antagonist atenolol, and the specific beta 2-adrenergic antagonist butoxamine were administered intraperitoneally (IP) to ovariectomized female rats in order to determine the role of beta-adrenergic receptors in drinking. D,l propranolol and atenolol administered at doses of 6, 12, and 18 mg/kg significantly attenuated the one-hour water intakes of rats administered angiotensin II (200 micrograms/kg, SC) and the water intakes of rats deprived of water for 24 hours. D propranolol, which has little beta-adrenergic blocking ability, administered at doses of 6 and 12 mg/kg, and butoxamine, administered at doses of 25 and 35 mg/kg, had no significant effects on the water intakes of angiotensin II treated or water deprived rats. Regardless of the dose, d,l propranolol, atenolol, and butoxamine failed to significantly alter the water intakes of rats administered 1.0 M NaCl (10 ml/kg, IP) The results provide evidence that beta 1-adrenergic receptors, but not beta 2-adrenergic receptors, are involved in mediating the increased water intakes induced by angiotensin II and water deprivation. On the other hand the increased water intake due to administration of hypertonic saline does not appear to mediated by beta-adrenergic receptors.     

FAILURE OF CAPTOPRIL TO LOWER BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS OFFERED WATER AND SALINE TO DRINK

The hypotensive action of chronic oral captopril treatment (50 mg/kg per day) was examined in two groups of male spontaneously hypertensive rats (SHR) of the Okamoto strain, one group offered a choice of water and 0.9% saline as drinking fluid, the other offered water alone, a third group of SHR, offered a choice of water and 0.9% saline, were treated with vehicle (0.9% saline, 2 ml/kg per day). Captopril treatment, over ten days, significantly lowered blood pressure in the group drinking water only but failed to significantly alter the blood pressure of SHR drinking a choice of water and 0.9% saline. Vehicle treatment did not alter the blood pressure of SHR drinking a choice of saline and water. In an identical experiment using male, genetically hypertensive rats (GHR) of the Smirk strain, captopril lowered blood pressure to the same extent in GHR drinking either a choice of water and 0.9% saline or water alone. In conclusion, the reported exaggerated saline preference of the spontaneously hypertensive rat appears to antagonize the hypotensive action of captopril.     

EFFECT OF ENALAPRIL ON HANDLING OF A SODIUM CHLORIDE LOAD BY GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

1. Enalapril was given in the drinking water (300 mg/L) for 4.5 days to normotensive (N) and genetically hypertensive (GH) rats on zero sodium intake. An intraperitoneal NaCl load was given 12 h after enalapril was started. 2. Enalapril did not increase the maximum rate of sodium excretion, but caused the rats to excrete more than the load in the first 24 h and then to have a slow fall in body sodium while on a sodium-free diet. 3. In terms of the Strauss et al. (1958) concept of body sodium, enalapril appears to lower the basal level. However, in addition it causes a slow leak of sodium which becomes apparent when sodium intake is very low.     

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [d-Ala²,MePhe⁴,Gly-ol⁵]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2–3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 µg) significantly decreased 0.6% saline intake; baseline water intake was low (3–5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 µg) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.     

Effects of neurotensin microinjected into ventral tegmental area on spontaneous motor activity in neonatal 6-hydroxydopamine-treated rats]

Intracerebroventricular treatment of the catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA) after desmethylimipramine pretreatment results in semipermanent brain dopamine (DA) depletion. It has been shown that rats neonatally treated with 6-OHDA show hyperactivity in an open-field test. The purpose of this study was to investigate the spontaneous motor activity in neonatal 6-OHDA-treated rats following bilateral saline (SAL; 0.25 microliter) or neurotensin (NT; 1.25, 2.50, 5.00 micrograms/0.25 microliter/side) microinjection into the ventral tegmental area. Each dose of NT significantly augmented locomotor activity in 6-OHDA-treated rats. On the other hand, controls did not show significant increase in lower dose of NT. Effect of NT microinjection on number of rearings in the 6-OHDA-treated group was not significantly altered compared to the vehicle-treated group. These results suggest that the responses in locomotor activity to NT the ventral tegmental area increase in neonatal 6-OHDA-treated rats, and imply that residual activity in mesolimbic DA neurons which is mediated by NT receptors contributes to a part of the hyperactivity seen after neonatal 6-OHDA lesion.     

The effect of para-chlorophenylalanine on the intake of ethanol and saccharin solutions.

The effects of para-chlorophenylalanine (PCPA) on the ingestive behavior of rats offered a choice between ethanol (3%) and water, saccharin (0.125%) and water, or water alone were examined. Following a baseline period three saline or PCPA injections, 80 mg/kg, were administered. Decreases in both ethanol and saccharin intakes were observed. Increases in water intake occurred in the ethanol group without a change in total fluid intake. Increases in water intake did not occur in the saccharin group and these animals displayed decreases in total fluid intake. Water intake in the nonchoice group was unaffected. There were no changes in food intake associated with any of these effects. The data demonstrate that decreases in intakes following PCPA are not specific to ethanol solutions.     

Effects of sub-chronic antipsychotic drug treatment on body weight and reproductive function in juvenile female rats

Rationale Weight gain caused by some antipsychotics is not only confined to adults but can also adversely affect both children and adolescents. Indeed, olanzapine and risperidone have been associated with extreme weight gain in adolescents even greater than that reported in adults. We have recently shown substantial weight gain in adult female rats following treatment with olanzapine and risperidone but not ziprasidone. Objectives The aim of the present study was to compare the effects of several antipsychotics on weight gain and reproductive function in juvenile (aged 7 weeks) female hooded Lister rats. Methods Olanzapine (4 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), sulpiride (10 mg/kg), haloperidol (0.5 mg/kg) or vehicle was administered i.p. once per day for 21 days. Body weight, food and water intake were measured daily, in addition to the determination of stage of the oestrous cycle. Results Sub-chronic administration of olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone, significantly increased body weight compared to vehicle-treated animals during weeks 1–3. Sulpiride significantly increased food and water intake. Significantly increased percentage intra-abdominal fat weight was observed in olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone-treated animals. Marked disruption of the oestrous cycle was observed in all but the ziprasidone-treated group, which continued to have regular 4-day oestrous cycles. Conclusions Weight gain observed in these juvenile animals was 1.5–2 times greater than that previously observed in adult rats. These findings have important implications for the use of antipsychotics in children and adolescent patients.     

STEREOLOGICAL STUDIES ON MESENTERIC RESISTANCE ARTERY STRUCTURE IN NEW ZEALAND GENETICALLY HYPERTENSIVE AND CONTROL RATS

1. Stereological methods were used to quantitate and compare the structure of mesenteric resistance arteries (MRA) in New Zealand genetically hypertensive (GH) rats aged 4, 10 and 16 weeks and their normotensive control strain (N). 2. Blood pressure (BP) (tail-cuff and intra-arterial) were recorded before the vessels were fixed by perfusion and embedded in Technovit Kulzer GmbH D-6393, Wehrheim, Germany). 3. Media and lumen volumes were measured on transverse sections (TS), by the Cavalieri method, and numbers of smooth muscle (SM) cells were estimated by the optical disector method. 4. There were no significant differences in lumen volume per unit vessel length between GH and age-matched N groups at any age. However, at 10 and 16 weeks volume in GH groups was 9–10% lower than their respective N groups. 5. Media volume per unit vessel length increased in GH rats at all ages. The media/lumen ratio also increased in GH at all ages. 6. Smooth muscle cell density (SM cell number per unit volume of media) decreased in GH rats at all ages, i.e. there was no evidence of hyperplasia. 7. Blood pressure (tail-cuff and intra-arterial) significantly increased in GH rats at 4 weeks of age and also at 10 and 16 weeks. 8. These results show that media volume is increased in GH early in life, is not due to hyperplasia, but may be due to hypertrophy of the SM cells, an increase in the amount of extracellular matrix or a combination of both. However, since hypertension is also present at an early age, structural abnormalities cannot be said to be a primary cause of GH hypertension.     

Reduction of fat and protein intakes but not carbohydrate intake following acute and chronic fluoxetine in female rats.

Fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, leads to reductions in food intake and body weight and is under investigation as a possible treatment for obesity. Additionally, it has been suggested that fluoxetine administration could lead to a selective suppression in carbohydrate consumption. Because women more often than men seek weight reduction treatment, the present study examined the acute and chronic effects of fluoxetine on food intake, macronutrient selection, body weight, estrous cycle, and motor activity in female rats. Female Long-Evans rats were provided with separate sources of protein, fat and carbohydrate, and nutrient intakes were recorded following single (5.0, 10.0, and 20.0 mg/kg, IP) and chronic daily (10 mg/kg for 28 days) injections of fluoxetine. Acute and chronic administration of fluoxetine significantly reduced total caloric intake when compared to vehicle treatment. Moreover, fluoxetine significantly suppressed fat and protein intakes, but not carbohydrate intake following both acute and chronic drug administration. Animals chronically treated with fluoxetine gained significantly less weight than animals treated with vehicle. Chronic fluoxetine treatment did not significantly alter estrous cycle. However, in both fluoxetine- and vehicle-treated animals, total caloric intake, and carbohydrate and protein intakes were reduced and fat intake was increased when estrogen levels were high. Fluoxetine significantly reduced motor activity up to 4 h postinjection, and increased motor activity 24 h postinjection.     

EFFECTS OF CILAZAPRIL ON THE STRUCTURE OF MESENTERIC RESISTANCE ARTERIES OF NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE CONTROL RATS

1. New Zealand genetically hypertensive (GH) rats and their normotensive controls (N) rats between the ages of 10 and 16 weeks were treated with cilazapril in the diet for 6 weeks. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly and intra-arterial blood pressure (BP) was measured at the end of the treatment period. 3. The effect of cilazapril on the structure of mesenteric resistance arteries (MRA) was evaluated by both stereological and myographic techniques. 4. Cilazapril lowered SBP significantly throughout the treatment period (16 weeks; GH with cilazapril 135 ± 5 vs GH 216 ± 9 mmHg, P < 0.001; N cilazapril 91 ± 6 vs N 137 ± 3 mmHg, P < 0.001); intra-arterial BP was also significantly lowered. 5. Bodyweight (BW) of treated GH rats was significantly lower than that of untreated GH at 16 weeks (P < 0.01; t-test); however, the weight of treated N rats was not significantly affected. Ventricular mass was reduced by cilazapril in GH and N rats (GH 259 ± 10 vs 306 ± 11, P < 0.001; N 171 ± 3 vs 195 ± 4 mg/100g BW, P < 0.001). 6. Lumen volume of MRA was not significantly affected by cilazapril in either strain; media volume was reduced by 14% in both strains and the media/lumen ratio was significantly reduced. Vascular smooth muscle cell density significantly increased in cilazapril-treated GH rats.     

The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats

This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.